The increase in the prevalence of obesity and related conditions such as type 2 diabetes mellitus (DM-2) and cardiovascular disease has taken place despite a decrease in the percentage of energy intake derived from daily dietary fat over the last 20 years. This observation suggests that factors other than dietary fat intake may be responsible for the observed increase in obesity and associated conditions. One such factor regulating weight and also directly influencing the morbidity and mortality associated with obesity is the dietary glycemic index (GI). In this study, we propose to investigate the association of dietary GI with intermediary predictors of long-term health outcomes related to DM-2 and its associated increased cardiovascular disease. In a 1-year weight loss study, we will compare two caloric restricted interventions providing 70 percent of baseline energy requirements of variable GI (20 percent fat and moderate GI vs. 35 percent fat and low GI) in 32 healthy men and women aged 30-40 years with initial values for body mass index (BMI) of 25-34.9 kg/m2. The following single-blinded outcome measurements will be made at baseline and at 1, 4, 8 and 12 months: (A) Body composition (fat, fat free mass and truncal/total fat) will be determined by dual x-ray absorptiometry (DXA). (B) Markers related to DM-2: central adiposity (truncal/total fat) by DXA and by Waist-Hip-Ratio, daily glucose average by 72-hour Continuous Glucose Monitoring System (CGMS), Hemoglobin A1c, Insulin Sensitivity and serum TNF-alpha levels. (C) Markers related to CVD: systolic and diastolic blood pressure, lipid profile (total cholesterol, HDL, triglycerides, LDL), plasma levels of fibrinogen, PAI-1, C-reactive Protein and serum Interleukin-6. We anticipate that this study will provide important new information that will have practical implications for both further scientific inquiry as well as clinical applications. Specifically: Identification of an acceptable intervention that promotes long-term weight loss and is associated with decrease in the morbidity and mortality associated with obesity and the metabolic syndrome will be an important development for public health. In relation to this suggestion, one of the important questions in dietary composition - energy regulation research currently is whether diets that are both high in fiber and low in GI are more beneficial that diets that are high in fiber without consideration of GI.